Strip package for antiseptic cap

ABSTRACT

A syringe assembly includes (1) a syringe barrel defining a chamber; (2) a plunger mounted in the chamber and moveable with respect to the barrel; and (3) a cap assembly containing a cap and an absorbent material is removably attached to the plunger. A strip package includes at least two cap assemblies. Each of the cap assemblies includes a cap holder and an antiseptic cap positioned in the cap holder. The antiseptic cap includes a sidewall defining a chamber and an antiseptic substance within the chamber. A strip extends over at least two cap assemblies. The strip includes a first seal engaged to the cap holder and a second seal engaged to the antiseptic cap.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 14/703,134, filed on May 4, 2015, now U.S. Pat. No.10,046,156, which claims the priority of U.S. Provisional ApplicationSer. No. 61/987,981, filed May 2, 2014, the entire disclosure of each ofwhich is expressly incorporated herein by reference in its entirety.

BACKGROUND

Technical Field

The present invention relates to an antiseptic cap having a thread coverto enhance a seal between the cap and an access site to a body of amammal. More particularly the invention relates to an antiseptic cap forattaching to an access site of an indwelling, central venous catheterand having a thread cover to enhance a seal between the cap and theaccess site.

Background Art

Catheters are widely used to treat patients requiring a variety ofmedical procedures. Catheters can either be acute, or temporary, forshort-term use or chronic for long-term treatment. Catheters arecommonly inserted into central veins (such as the vena cava) fromperipheral vein sites to provide access to a patient's vascular system.Catheters offer many advantages for patients; for example, chroniccatheters provide ready access without repeated punctures or repeatedvessel cannulation for administration of large volumes of fluids,nutrients and medications and for withdrawal of blood on an intermittentbasis. With respect to the use of catheters for infusion of fluids,examples include the infusion of drugs, electrolytes or fluids used inchemotherapy. In chemotherapy, catheters are used for infusion of drugson an intermittent basis, ranging from daily to weekly. Another exampleincludes the use of catheters in hyperalimentation treatment, whereinthe catheters are usually used for infusion of large volumes of fluids.

For hemodialysis, catheters are commonly used—usually three times perweek—for aspiration of blood for dialysis treatment and rapid return ofthe blood to circulation after treatment. Although a preferred mode ofvascular access for a hemodialysis patient involves using anarteriovenous (AV) fistula of either the upper or lower extremities oran arteriovenous “bridge” graft (typically utilizing PTFE), use of theseaccess devices is not always possible or desirable. When either of thesemodes of vascular access is not available, for example, due to a paucityof adequate blood vessels for creation of AV “shunts” or due tononoptimally functioning established AV shunts, a large bore venous linecatheter is typically required for hemodialysis. Catheters used forhemodialysis usually include two relatively large diameter lumens(usually molded as one catheter) for aspiration and rapid return ofblood required during the hemodialysis procedure. One lumen of such acatheter is used for aspiration, or removal, of blood, while the otherlumen is used for returning the blood to the patient's bloodstream.

Catheter connections, such as, for example, connections of catheters todialysis machine tubing, to IV line tubing, to infusion ports and tocatheter caps, which are used to seal the end of a catheter to protectthe sterility of the catheter and prevent fluid loss and/or particlecontamination, are most often made utilizing the medical industry'sstandardized Luer taper fittings. These fittings, which may either bemale couplings or female couplings, include a tapered end ofstandardized dimensions. Coupling is made by the press-fit of matingparts. A threaded lock-fit or other type of securing mechanism iscommonly utilized to ensure the integrity of the pressure fit of theLuer fittings.

Catheters, especially chronic venous catheters, provide challenges intheir use. One such challenge is that such catheters can become occludedby a thrombus. In order to prevent clotting of catheters in bloodvessels between uses, such as, for example, between dialysis treatmentswhen the catheter is essentially nonfunctioning and dwells inside a“central” vein (i.e. superior vena cava, inferior vena cava, iliac,etc), the lumens of the catheter are often filled with a lock solutionof a concentrated solution of the commonly used anticoagulant, heparin(up to 10,000 units of heparin per catheter lumen).

As used herein, the terms “lock solution” or “locking solution” refer toa solution that is injected or otherwise infused into a lumen of acatheter with the intention of allowing a substantial portion of thelock solution to remain in the lumen and not in the systemic bloodcirculation until it is desired or required to access that particularlumen again, typically for additional treatment, i.e., infusion orwithdrawal of fluid. In addition, attention has been given to thedevelopment of alternative lock solutions with the goal of improving thepatency rates of vascular catheters. For example, lower-alcoholcontaining locking solutions are under development wherein the loweralcohols include ethanol, propanol and butanol. Anti-microbial and/oranticoagulant additives can optionally be added to the lower-alcoholcontaining locking solution. Preferably the lock solution can remain inthe lumen for a desired amount of time lasting from about 1 hour to 3 or4 days or longer.

For the reasons set forth above, significant care must be taken wheninfusing medications, nutrients and the like into a catheter, and when“locking” a catheter between uses, to minimize the risks associated withan indwelling catheter, including the risk of thrombosis or clotting,the risk of excessive anticoagulating and the risk of infection.Syringes are typically used to administer the required amount ofcatheter lock solution (determined by the catheter manufacturer) into anindwelling catheter after a given use. Flush procedures also requirethat care be taken to prevent blood reflux into the catheter. Reflux inIV therapy is the term commonly used to describe the fluid that is drawnback into the catheter after a flush procedure. The concern is that thereflux fluid contains blood or solution that could cause the catheter toocclude. To ensure that reflux does not occur, flush procedures suggesttwo techniques: 1) at the end of the flush solution delivery, the usermaintains pressure on the syringe plunger while clamping the IV line; or2) while delivering the last 0.5 ml of flush solution disconnect thesyringe from the IV port or clamp the IV line. Either techniquemaintains positive pressure on the fluid in the catheter to preventreflux of fluid and blood.

In light of the above-described problems, there is a continuing need foradvancements in catheter lock techniques, devices and procedures toimprove the safety and efficacy of catheter locking procedures and ofoverall patient care.

SUMMARY

In accordance with the present disclosure, a package for a cap assemblyis provided. The package includes an outer seal engaged to a cap holder,and an inner seal arranged substantially concentric with respect to theouter seal. The inner seal engaged to an antiseptic cap positioned inthe cap holder.

In accordance with an embodiment, a strip package includes at least twocap assemblies. Each of the cap assemblies includes a cap holder and anantiseptic cap positioned in the cap holder. The antiseptic cap includesa sidewall defining a chamber and an antiseptic substance within thechamber. A strip extends over at least two cap assemblies. The strip hasa sterile cover. The strip includes a first seal engaged to the capholder and a second seal engaged to the antiseptic cap. In anotherembodiment, the strip includes a single seal engaged to the cap holder.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an antiseptic cap equipped plunger andsyringe barrel assembly prior to connection of a syringe tip to anaccess point to a central venous catheter;

FIG. 2 is a perspective view of an antiseptic cap equipped plunger andsyringe barrel assembly with the syringe tip connected to an accesspoint to a central venous catheter;

FIG. 3 is a perspective view of an antiseptic cap equipped plunger andsyringe barrel assembly prior to connection of the antiseptic cap to anaccess point to a central venous catheter;

FIG. 4 is a perspective view of an antiseptic cap equipped plunger andsyringe barrel assembly after connection of the antiseptic cap to anaccess point to a central venous catheter;

FIG. 5 is a perspective view assembly drawing of an antiseptic capequipped plunger;

FIG. 6 is a perspective view of an antiseptic cap equipped plunger m apartially assembled state;

FIG. 7 is a perspective view of the antiseptic cap equipped plunger ofFIG. 6 with a top seal;

FIG. 8 is a perspective view of an antiseptic cap equipped plunger ofFIG. 7 mounted in a lumen of a syringe barrel;

FIG. 9 is a side view in cutaway of an antiseptic cap equipped plungerand syringe barrel assembly;

FIG. 10 shows an exploded view of a detail of FIG. 9 of one embodimentof the antiseptic cap equipped plunger and syringe barrel assembly;

FIG. 11 shows an exploded view of a detail of FIG. 9 of anotherembodiment of the antiseptic cap equipped plunger and syringe barrelassembly;

FIGS. 12-14 show various embodiments of grips of the antiseptic capequipped plunger assembly;

FIGS. 15-17 show various views of one embodiment antiseptic cap equippedplunger and syringe barrel assembly with a barrel lock to resistrotation of the plunger assembly with respect to the syringe barrel;

FIG. 18 shows another embodiment of a barrel lock to resist rotation ofthe plunger assembly with respect to the syringe barrel;

FIGS. 19-20 show various views of another embodiment antiseptic capequipped plunger and anti-reflux syringe barrel assembly with a barrellock to resist rotation of the plunger assembly with respect to thesyringe barrel;

FIG. 21 shows a perspective view of another embodiment antiseptic capequipped plunger and syringe barrel assembly with a barrel lock toresist rotation of the plunger assembly with respect to the syringebarrel;

FIGS. 22 a, b are respectively a perspective view of an antiseptic capwithout a sponge and with a sponge;

FIGS. 23 and 24 are different embodiments of the antiseptic cap withvarying gripping features;

FIG. 25 is a perspective view of the antiseptic cap of FIG. 22b prior todocking with a valve;

FIG. 26 is a perspective view of the antiseptic cap of FIG. 22b dockedwith a valve;

FIG. 27 is a side view in cutaway of the antiseptic cap and valveassembly shown in FIG. 26;

FIGS. 28-30 are side views in cutaway of two different embodiments ofthe antiseptic cap;

FIGS. 31 a, b are, respectively, side views in cutaway showing anantiseptic cap with a centrally disposed actuation post mounted on avalve with the valve in the unactivated and activated positions;

FIGS. 32 and 33 are side views in cutaway showing two differentembodiments of an antiseptic cap having a molded sponge;

FIG. 34 is a side view in cutaway showing another embodiment of anantiseptic cap having a molded sponge docked to a valve;

FIG. 35 is a side view in cutaway showing a step of attaching a moldedsponge to an antiseptic cap;

FIG. 36 is a side view in cutaway showing a step of delivering anantiseptic compound to a molded sponge positioned within a cap;

FIG. 37 shows a side view in cutaway of an antiseptic cap docking to avalve with the antiseptic cap having an antiseptic coating;

FIG. 38 shows a perspective view of an antiseptic cap in a blisterpackage;

FIG. 39 is a side cross-sectional view of an antiseptic cap with athread cover;

FIG. 40 is a side cross-sectional view of an antiseptic cap with athread cover;

FIG. 41 is a side cross-sectional view of an antiseptic cap with athread cover;

FIGS. 42 a, b are perspective front and back views of an antiseptic capwith a thread cover connected to a Cardinal SMART SITE access site;

FIGS. 43 a, b are perspective front and back views of an antiseptic capwithout a thread cover connected to a Cardinal SMART SITE access site;

FIGS. 44 a, b are perspective front and back views of an antiseptic capwith a thread cover connected to a Hospira (ICU) C1000 Clave accessdevice;

FIGS. 45 a, b are perspective front and back views of an antiseptic capwithout a thread cover connected to a Hospira (ICU) C1000 Clave accessdevice;

FIGS. 46 a, b are perspective front and back views of an antiseptic capwith a thread cover connected to a B. Braun ULTRASITE access device;

FIGS. 47 a, b are perspective front and back views of an antiseptic capwithout a thread cover connected to a B. Braun ULTRASITE access device;

FIGS. 48 a, b are perspective front and back views of an antiseptic capwith a thread cover connected to a Rymed INVISION PLUS access device;

FIGS. 49 a, b are perspective front and back views of an antiseptic capwithout a thread cover connected to a Rymed INVISION PLUS access device;

FIG. 50 is a side cross-sectional view of an antiseptic cap with athread cover connected to a Cardinal SMARTSITE PLUS access device;

FIG. 51 is a side cross-sectional view of an antiseptic cap with athread cover connected to a Cardinal SMARTSITE PLUS access device andthe thread cover having a reduced diameter when compared to the threadcover shown in FIG. 50;

FIG. 52 is a side cross-sectional view of an antiseptic cap with athread cover connected to a Hospira (ICU) C1000 Clave access devicehaving a thread cover with an alternative profile;

FIG. 53 is an assembly view of an antiseptic cap and cup holder equippedplunger and syringe barrel system;

FIG. 54 is an assembly view of a cup-holder-antiseptic cap assemblyadjacent a plunger and syringe barrel system;

FIG. 55 is a side view in cross-section of an antiseptic cap and cupholder equipped plunger and syringe barrel assembly;

FIG. 56a is a perspective view of a medical access device adjacent anantiseptic cap equipped plunger and syringe barrel assembly with a lidstock peeled back in preparation for docking;

FIG. 56b is a perspective view of a medical access device docked to anantiseptic cap equipped plunger and syringe barrel assembly;

FIG. 56c is a perspective view of a medical access device docked to anantiseptic cap adjacent a plunger and syringe barrel assembly;

FIG. 57 is an enlarged view of a cup holder and antiseptic cap assemblyadjacent an open and empty chamber of a syringe plunger;

FIG. 58 is an enlarged view of a cup holder and antiseptic cap assemblypositioned within a chamber of a syringe plunger;

FIG. 59 is a perspective view of an alternative embodiment of anantiseptic cap assembly adjacent a syringe plunger and barrel assembly;

FIG. 60 is a perspective view of an alternative embodiment of anantiseptic cap assembly docked to a syringe plunger and barrel assembly;

FIG. 61 is a perspective view of an alternative embodiment of anantiseptic cap assembly docked to a syringe plunger and barrel assemblywith an outer wall being transparent to reveal interior portions of theassembly;

FIG. 62 is a top view of a strip package for antiseptic cap holderassemblies;

FIG. 63 is a cross-sectional view taken along line A-A of FIG. 62;

FIG. 64 is a side view of the strip package; and,

FIG. 65 is an enlarged view taken at location “B” of FIG. 63.

DETAILED DESCRIPTION

While this invention is susceptible of embodiment in many differentforms, there is shown in the drawings, and will be described herein indetail, specific embodiments thereof with the understanding that thepresent disclosure is to be considered as an exemplification of theprinciples of the invention and is not intended to limit the inventionto the specific embodiments illustrated.

FIGS. 1 and 2 show an antiseptic cap equipped plunger and syringe barrelassembly 10 having an antiseptic cap equipped plunger (or piston)assembly 12 and a syringe barrel 14. The barrel 14 has a side wall 16defining a chamber 18 and the barrel has a proximal end 20 and a distalend 22. The proximal end 20 has an opening 23 to the chamber 18 and aflange 24 extending radially outwardly from the wall 16. The flange 24has upper and lower surfaces 26, 28 and provides gripping surfaces foran user of the assembly 10. The distal end 22 of the barrel 14 has anend wall 30 and an elongate tip 32 extending distally therefrom andhaving a passageway 34 therethrough and in fluid communication with thechamber 18. The distal end wall 30, in one preferred form of theinvention, is generally conically shaped and, as is well known in theart, can have a locking luer collar 35 concentrically surrounding thetip 32 and having a set of threads 37 on an inside surface thereof. Theluer collar 35 allows for attaching a needle or a cannula to barrel 14and for docking the assembly 10 to mating threads located on otherdevices such as valves, injection sites and other medical access deviceswell known in the art. FIG. 1 shows the syringe assembly proximate anaccess site 38 having a valve 39 controlling access to a lumen of atubing 41.

In one preferred form of the invention the chamber 18 of the syringeassembly 10 will be filled with a locking solution or a flush solutionfor use with an indwelling, central venous catheter. The manner of usinga locking or flush solution with a catheter is well known in the art.Suitable locking or flushing solutions will be set forth below. Theflush or locking solution is injected into a fluid access site of thecatheter to clean and disinfect the catheter and can be withdrawn fromthe catheter or allowed to remain in an end portion of the catheter toserve as a barrier to the ingress of pathogens and contaminants.

The antiseptic cap plunger assembly 12 has an elongate shaft 40, aproximal end 42 and a distal end 44. The elongate shaft 40, in onepreferred form of the invention, is generally cruciform incross-sectional shape. A stopper or piston 50 is connected to the distalend 44 of the plunger 40. The piston 50 is dimensioned such that wheninserted into the syringe barrel chamber 18 an outer circumferentialsurface of the piston 50 is in fluid-tight engagement with an innersurface 54 of the syringe barrel. The piston assembly 14 when movedproximally (or when being withdrawn) can draw fluid into the chamber andwhen moved distally (or when inserted into the syringe chamber) candrive fluid out of the chamber. FIG. 1 shows the piston assembly 12partially inserted into the syringe chamber and FIG. 2 shows the pistonassembly fully inserted into the syringe chamber to deliver fluid to thetubing 41.

A housing 60 is located at the proximal end 42 of the plunger assembly12 and has a wall 62 defining a chamber 64 having an open end 66 whichcan be sealed by any suitable structure or material such as a cap or bya foil material 68. An optional annular flange 70 extends radiallyoutwardly from the wall 62 and provides a surface upon which the sealingstructure can be attached.

FIG. 5 shows a cap assembly 80 proximate the chamber 64 of the housing60 and FIG. 6 shows the cap assembly 80 positioned within the chamber64. In one preferred form of the invention, the cap assembly 80 has acap 82 having a wall 83 defining a chamber 84 containing an absorbentmaterial 86 such as a sponge. The sponge 86, in a preferred form of theinvention, is wetted or soaked with an agent such as an antiseptic,anticoagulant or antimicrobial (“antiseptic solution”) and can beselected from the locking and flushing solutions set forth below or theantiseptic solutions set forth below. The cap 82 has an interior surface87 with a set of threads 88 for mating with a set of threads on theaccess site 38.

FIGS. 7 and 8 show the cap assembly 80 sealed with a foil material orlid stock material 68 which can be attached to the flange 70 by anysuitable method such as by adhesives or by conductive or inductive heatsealing techniques. FIG. 7 shows the antiseptic cap piston assembly 12and FIG. 8 shows the antiseptic cap equipped piston assembly 12 insertedinto the chamber of the syringe barrel 14 to define the antiseptic capequipped piston and syringe barrel assembly 10.

FIGS. 3 and 4 show one possible method for utilizing the cap assembly 80by docking with the access device 38. FIG. 3 shows the lid stock 68pealed away from the flange 70 and FIG. 4 shows docking the antisepticcap assembly 80 to the valve 39. The syringe barrel is rotated clockwiseor counterclockwise to engage the threads 88 of the antiseptic capassembly 80 with the threads of the access site 38. After engagement,the syringe barrel 14 will be moved away from the access site 38 and theantiseptic cap assembly 80 will slide outward from the housing 60 andremain docked to the access site 38. The antiseptic cap assembly 80 canremain docked to the valve 39 of the access site 38 for any suitableperiod of time from a few minutes to numerous hours. When the antisepticcap assembly 80 is docked to the valve 39 the tubing or catheter 41 issealed to block the ingress into the catheter of pathogens andcontaminants and a portion of the access site 38 is exposed to theantiseptic material in the sponge 86.

It is desirable that during the rotation of the syringe barrel that theantiseptic cap assembly 80 does not rotate with respect to the housingand/or optionally that the plunger assembly 12 does not rotate withrespect to the syringe barrel 14 until the threads 88 of the antisepticcap can fully engaged the threads of the access site 38. The presentinvention provides a mechanism associated with the assembly 10 forpreventing the rotation of the antiseptic cap assembly 80 with respectto the plunger assembly 12 and more preferably a mechanism on either theplunger assembly or on the antiseptic cap 80 to prevent relativerotational movement between the antiseptic cap 80 and the plungerassembly 12. In an even more preferred form of the invention, themechanism for preventing relative rotation of the antiseptic capassembly 80 with respect to the plunger assembly 12 has mating portionson both parts that when assembled cooperatively engage one another toprevent relative rotation. It is also contemplated that a separatemechanism, device or member could be used to lock the two parts togetherto achieve this purpose.

If an user grasps the assembly 10 by the antiseptic cap and plungerassembly 12 then the interlocking structures between the plungerassembly 12 and the syringe barrel 14 would not necessarily be needed.Accordingly, FIGS. 5, 9-11 show exemplary structures for locking theantiseptic cap assembly 80 inside the housing 60 so that these partsrotate together and one part does not rotate in a direction or at a ratedifferent from that of the other part. Further, FIGS. 15-18 showexemplary structures for interlocking the antiseptic cap plungerassembly 12 with the syringe barrel 14.

In one preferred form of the invention the housing 60 will have afeature or structure that forms an interference fit with an externalsurface 83 of the antiseptic cap 80. Even more preferable, an internalsurface 63 of the side wall 62 of the housing 60 will have a feature orstructure to form an interference fit with a portion of the antisepticcap assembly 80. In another preferred form of the invention theantiseptic cap assembly 80 will have a feature to form an interferencefit with the housing 60 and even more preferably the outer surface 83 ofthe antiseptic cap 80 will have a feature to contact the inner surface63 of the housing side wall 62.

In another preferred form of the invention the plunger housing 60 andthe cap assembly 80 each will have a feature or structure thatcooperatively engage one another to prevent relative rotation of the capassembly 80 and the housing 60. FIG. 5 shows one preferred form of theinvention having a plurality of circumferentially spaced and axiallyextending ribs 100 on the internal surface 63 of the housing side wall62 (internal ribs 100) for engaging the wall 83 of the antiseptic cap 82to lock the cap assembly 80 in place to prevent rotation of the capassembly 80 when positioned inside the housing 60. In a preferred formof the invention, the internal ribs 100 extend from a bottom wall 102 upto an intermediate height of the housing sidewall 62. In a preferredform of the invention the internal ribs 100 will have a height roughlyequal to a height of the cap 82. A plurality of internal slots 108 aredefined between each set of adjacent internal ribs 100. The internalribs 100, in a preferred form of the invention, will have a width thattapers inwardly from proximate the bottom wall 102 to a top 104 of theinternal ribs 100 so that the width of the internal ribs decrease from abottom 106 of a rib to the top 104 of the rib. Also, it is preferablethat the top of the internal ribs 100 have a generally arcuate profileto act as a lead-in during insertion of the antiseptic cap assembly 80into the housing 60. In a preferred form of the invention, the internalribs 100 will terminate short of a top 113 of the housing sidewall 62 todefine an annular gap 111 between the top of the rib 104 and the top113. Also, extending radially inwardly from the internal surface 63 ofthe cap 82 is a detent 109 positioned proximate a top portion 113 of theside wall 62.

The antiseptic cap 82 has a plurality of circumferentially spaced andaxially extending ribs 120 extending along an external surface 121 ofthe cap 83 of cap 82 (external ribs 120). In one preferred form of theinvention external ribs 120 extend between annular flange 123 at aproximal end 124 of the cap 82 to a position proximate a distal end 126of the cap 82. The external ribs 120 are dimensioned for engaging aportion of the interior wall surface 63 of the housing 62 to preventrelative rotation of the cap assembly 80 and the plunger assembly 12.Spacing between the external ribs define a plurality of external slots122 between each adjacent pair of external ribs 120. When the cap 82 ispositioned within the chamber 64 (FIGS. 9 and 11) each of the externalribs 120 are positioned within an internal slot 108 and each of theinternal ribs 100 are positioned within an external slot 122 to locktogether these parts to assure that the cap rotates in the samedirection as the plunger rod assembly 12. FIGS. 6 and 11 also show thatwhen the cap 82 is positioned within the housing 60, the detent 109contacts the annular flange 123 to hold the cap assembly 80 in theplunger housing chamber 64 to prevent or resist inadvertent dropping ofthe cap assembly 80 from the housing chamber 64 prior to docking of thecap assembly 80 with the access site 38.

FIGS. 12-14 show several embodiments of gripping surfaces on the housing60 (with lid stock 68 removed) to facilitate use of the assembly 10 orthe plunger assembly 12. FIG. 12 shows axially extending andcircumferentially spaced protuberances 130 on an outer surface of thewall 62. The protuberances 130 can have numerous differentcross-sectional shapes including circular, polygonal, oval and irregularand, in a preferred form of the invention, extend from the flange 70 toa bottom of the housing.

FIG. 13 shows a housing 60 that has no flange 70 and has protuberances130 on the wall 62 extending substantially the entire height of thehousing 60. FIG. 14 shows a housing 60 where the outer surface of thewall 62 is relatively smooth but has a series of circumferentiallyspaced and axially extending protuberances 130 on a circumferential edgeof the flange 70.

As with the cap and plunger assembly rotational locking features orstructures, the optional plunger assembly 12 and syringe barrel 14locking feature or structure can be positioned alone on the plungerassembly 12, or alone on the syringe barrel 14 or have cooperatingstructures on both the plunger assembly 12 and the syringe barrel 14. Itis also contemplated that a separate mechanism, device or member couldbe used to lock the two parts together to achieve this purpose.

FIGS. 15-18 show various embodiments for the optional feature of lockingthe plunger assembly 12 from rotational motion with respect to thesyringe barrel 14. In one embodiment shown in FIGS. 15-17 and 21 a wing150 extending axially along an outside surface of the housing side wall62 engages a tooth 152 positioned on an interior surface of the syringebarrel 14 at its proximal end 20. More preferably, the plunger assembly12 will have more than one wing 150 with each wing beingcircumferentially spaced from the other. In an even more preferred formof the invention the plunger assembly will have four wings 150 spaced 90degrees from one another. Also, in a more preferred form of theinvention, the syringe barrel 14 will have a plurality ofcircumferentially spaced teeth 152. When the plunger assembly 12 isnearly fully inserted into the syringe barrel 14 each of the wings 150will extend into a tooth 152 to prevent rotation of the plunger assembly12 with respect to the syringe barrel 14.

FIG. 18 shows another embodiment of a locking feature to preventrotation of the plunger assembly 12 with respect to the syringe barrel14 and also prevents relative translational motion of the parts. In thisembodiment an annular protuberance 160 positioned on an interior surfaceof the syringe barrel at its proximal end 20 engages an annular detent162 on an outside surface of the plunger rod.

FIGS. 19 and 20 show an antiseptic cap equipped plunger assembly 12 andnon-refluxing syringe assembly 170. Non-refluxing syringes are wellknown in the art and there are numerous methodologies for reducingreflux while accessing the access site of a central venous catheter. Inthis embodiment the annular flange 70 of the plunger assembly 12 abutsthe flange 24 of the syringe barrel prior to the piston 50 contacting aninterior surface of the syringe distal end wall 30.

It is contemplated that the antiseptic cap assembly 80 of the presentinvention need not be coupled or combined with a plunger or a syringebarrel. FIGS. 22a,b show a stand-alone antiseptic cap assembly 200having three circumferentially spaced ribs 120 for grasping by the handof an user of the cap assembly. FIG. 22a shows the cap 82 without anabsorbent material 86 and FIG. 22b shows the cap with an absorbentmaterial. The cap 200 can be used for the same purposes of the capassembly 80 described above but will be used by hand. All other featuresof the cap 200 are essentially the same as described above with theexception that the cap 200 does not have to be dimensioned to fit withina chamber carried by a syringe plunger. FIGS. 23 and 24 show varyingfrequency of ribs 120 and varying shapes and sizes.

FIG. 25 shows the cap 200 proximate the access site 38 and FIGS. 26 and27 show the cap 200 docked to the access site 38.

A suitable absorbent material 86 includes medical grade materialscapable of storing and releasing an antiseptic liquid, or liquid havingother medical purposes, and includes materials such as sponges,rupturable capsules and other materials or devices capable of servingthis purpose. Suitable sponges can include any sponge suitable for usefor medical purposes and can be naturally occurring or synthetic. Thesponges can be die cut into suitable shapes or can be molded into thedesired shape. It is desirable that the sponge 86 be attached to theantiseptic cap 82 to prevent the sponge 86 from inadvertently fallingout of the cap 82. FIG. 28 shows the sponge 86 is captured between anannular wall 202 and a disc 204 attached to the cap 82 by any suitablemethod such as ultrasonic or vibrational welding or other techniqueswell known in the art.

FIGS. 29 and 30 show a variation on the cap assembly 200 of FIG. 28. Inthis embodiment, the sponge is retained in the cap 82 with a plasticsheet 206 heat welded to the cap. In one preferred form of the inventionthe sponge is attached by an adhesive or by other method to form anassembly which is then attached to the cap.

FIGS. 31 a, b show the cap 200 having a coaxially disposed and axiallyextending actuating post 220 circumferentially surrounded by a sponge 86having a centrally positioned hole to fit over the post 220. FIG. 31ashows the cap 200 in initial engagement with the access site 38 and FIG.31b shows the cap threaded onto the access site 38 and the actuatingpost opens the valve 39 and antiseptic fluid is allowed to flow into thevalve.

FIGS. 32-34 show varying shaped sponges that, in one preferred form ofthe invention, were molded into various desirable shapes. The sponge ofFIG. 34 has a central opening 230 to facilitate attaching the sponge tothe cap and to filling the sponge with antiseptic, anticoagulant orother suitable fluids set forth above. FIG. 35 shows the cap having acentrally disposed energy director 231, an ultrasonic welder 232 beingbrought into cooperative engagement with the sponge on a side of thesponge opposite the energy director 231. By applying ultrasonic energythe energy director 231 melts and attaches the sponge to the cap. FIG.36 shows a filling device 240, having a lumen 242 and a dispensing head244 in fluid communication with a source of antiseptic, anticoagulant orthe like for dispensing a metered amount of such fluid into the interiorportion of the sponge.

FIG. 37 shows an alternative embodiment of the antiseptic cap 200 wherethe sponge is replaced by an antiseptic coating on the actuating post220.

FIG. 38 shows the antiseptic cap 200 positioned in a blister pack 233prior to sealing the blister pack.

FIG. 39 shows an antiseptic cap 300 with a thread cover 302. The threadcover 302 can be part of any of the antiseptic caps discussed herein.The thread cover 302 is made of a deformable material capable of flexingupon application of moderate force applied by hand. In one preferredform of the invention the thread cover 302 is made from a polymericcontaining material and more preferably a polymeric material having amodulus of elasticity of less than 20,000 psi. In another preferred formof the invention the polymeric material will be an elastomer orplastomer or like material. The thread cover 302 enhances the connectionbetween the antiseptic cap 300 and a device such as a valve or otheraccess devices 38. The thread cover 302 provides a physical barrier tothe ingress of pathogens, dust or other contaminants through the matingthreads of the antiseptic cap 300 and the access device or valve towhich it is docked. The thread cover 302 also serves to retainantiseptic fluids from the antiseptic cap 300 from leaking out throughthe threads. The thread cover can be made a part of the antiseptic cap300 using techniques well known in the art such as overmolding, or byattaching as a separate part using welding techniques such as heatconductive welding, heat induction welding, vibrational welding, stretchor friction fit, or by using a suitable adhesive.

The thread cover 302 can provide a universal fit to most commerciallyavailable valves, connectors and access devices, or the thread cover 302can be customized to dock with a particular access device.

FIG. 39 shows, as is described above, the antiseptic cap 300 has anannular wall 305 having a first end 306 and a second end 320 with thefirst end having a greater diametrical dimension than the second end.The annular wall defines a central chamber 322 having an open end 323.In one preferred form of the invention, the chamber 322 will have asponge 86 positioned therein as shown in FIGS. 5 and 6 above, althoughit is not shown in FIG. 39. The thread cover 302 is shown attached by anoptional bonding layer 304 to the first end 306 of the annular wall 305.The thread cover 302 has a first leg 308 and a second leg 310. The firstleg 308 extends parallel to the annular wall 305 and the second leg 310extends radially inwardly from the annular wall 305 in a directiontransverse to the first leg 308 and across a portion of the open end 323and defines a central opening 312, having a reduced diameter whencompared to the open end 323, into the chamber 322. The second leg 310terminates at a distal end 330 with a rounded outer surface 332.

FIG. 40 shows an alternative embodiment of the antiseptic cap 300 havingthe thread cover 302 having both the first and second legs 308, 310attached to the first end 306 of the annular wall 305 through bondinglayers 304 a, b. A top surface 340 of the first end 306 is shown havingthe same thickness or diametrical dimension as the remainder of thefirst end but it is contemplated the top surface could have a radiallyextending flange 123 as shown in FIG. 5.

FIG. 41 shows an alternative embodiment of the antiseptic cap 300 thatdiffers from the antiseptic cap shown in FIGS. 39 and 40 by notincluding a counterbore 336 shown in these figures. The counterbore 336provides a chamber of reduced diameter and, therefore, will form atighter fit with access devices with a more narrow outer diameter whencompared to the cap shown in FIG. 41 which does not include thecounterbore. This is just one example of the modifications that can bemade to the geometry of the antiseptic cap to enhance the connectionbetween the cap and an access site.

FIGS. 42 a, b show front and back views of the antiseptic cap 300 withthe thread cover 302 connected to a Cardinal SMART SITE access site 350.FIGS. 43 a, b are perspective front and back views of the antiseptic capwithout the thread cover 302 connected to the Cardinal SMART SITE accesssite.

FIGS. 44 a, b are perspective front and back views of the antiseptic cap300 with the thread cover 302 connected to a Hospira (ICU) C1000 Claveaccess device 352. FIG. 45 a, bare perspective front and back views ofthe antiseptic cap, without a thread cover 302, connected to the Hospira(ICU) C1000 Clave access device.

FIGS. 46 a, b are perspective front and back views of the antiseptic cap300 with the thread cover 302 connected to a B. Braun ULTRASITE accessdevice 354. FIGS. 47 a, b are perspective front and back views of theantiseptic cap without the thread cover 302 connected to the B. BraunULTRASITE access device.

FIGS. 48 a, b are perspective front and back views of the antiseptic capwith the thread cover 302 connected to a Rymed INVISION PLUS accessdevice; 356. FIGS. 49 a, b are perspective front and back views of theantiseptic cap without the thread cover 302 connected to a RymedINVISION PLUS access device.

FIGS. 50-52 show various embodiments of the thread cover 302. FIG. 50differs from FIG. 51 in that the second leg 310 extends farther acrossthe opening of the chamber in FIG. 51 than shown in FIG. 50. FIG. 52shows another embodiment of the thread cover 302 having a segmentedsecond leg 310 a, b. This embodiment may be desirable to provide a moreeffective seal for certain access devices.

FIG. 53 shows an exploded view of an alternative embodiment 400 of thesyringe barrel assemblies 10, discussed above, incorporating a capholder 402 into the system of parts. Thus, the alternative assembly andsystem 400 has an antiseptic cap and cap holder equipped plungerassembly 12′, a syringe barrel 14, an antiseptic cap 82 (shown with anoptional thread cover 302), an absorbent material 86, and peelable lidstock 68. FIG. 54 shows an exploded view of an antiseptic cap holderassembly 404 including the cap holder 402 with the antiseptic capassembly 80 positioned within a chamber 406 of the cap holder 402. Thisembodiment 400 allows for the separate manufacture, assembly, andsterilization of the assembly 400 from the plunger assembly and thesyringe barrel.

The cap holder 402 has a proximal and distal ends 408, 410, and an innerwall surface 412 and an outer wall surface 414, an opening 416 into thechamber 406, and a radially outwardly extending flange 418 circumjacentthe opening 416 and extending from the proximal end 408 of the capholder 402. The cap holder 402 will also have an optional bottom wall419.

In a preferred form of the invention, the cap holder 402 or theantiseptic cap 82 will have a structure, element or the like thatprevents the relative rotation of the cap holder 402 and the antisepticcap 82 until the antiseptic cap assembly 80 is securely docked to theaccess device 38. Also, in a preferred form of the invention the capholder 402 or the plunger assembly 12′ will have a structure, element orthe like for preventing the relative rotation of the cap holder 402 andthe plunger assembly 12′ until the antiseptic cap assembly 80 issecurely docked to the access device 38. Any of the anti-rotationdevices discussed above to stop the rotation of the antiseptic capassembly 80 with the plunger assembly 12 would be suitable for, thesepurposes. Also, it is contemplated the devices discussed above inreference to FIGS. 15-21 to prevent the relative rotation of the plungerassembly 12 and the syringe barrel 14 could be incorporated into thisembodiment 400.

FIG. 53 shows the inner wall surface 412 of the cap holder 402 carriesthe internal ribs 100 and the internal slots 108 that interact with theexternal ribs and external slots 120, 122 of the cap 82 as is describedabove with respect to FIG. 5. These structures prevent or resist therelative rotation of the cap holder 402 with respect to the antisepticcap assembly 80. The term “ribs” referred to herein are structures thatare raised or extend outward from a surface. The term “slots” refer tostructures that extend below a surface or is defined between two ribsand is at a lower level than the ribs.

FIG. 53 also shows an interlocking structure for preventing the relativerotation of the cap holder 402, or the cap holder assembly 404, withrespect to the plunger assembly 12′. The outer wall surface 414 has aplurality of circumferentially spaced and axially extending ribs 420defining slots 424 between each pair of adjacent ribs. In a preferredform of the invention, the ribs 420 are generally triangular in shapehaving a base portion 426 and an apex portion 428. The slots 424 areoppositely-oriented triangularly shaped areas having slot base portions430 extending between two adjacent rib apex portions 428 and slot apexportions 432 separating adjacent rib base portions 426. On the internalwall surface 63 of the plunger chamber 64 are similarly shaped plungerribs 434 and plunger slots 436. The ribs 420 are dimensioned to fitwithin the plunger slots 436 and the slots 424 are dimensioned to fitover and receive the plunger ribs 434. Thus, when the cap holder 402 orthe cap holder assembly 404 is inserted in the plunger chamber 64 thecap holder ribs 420 are interdigitated with the plunger ribs 434 toprevent or resist the relative rotation of the cap holder 402, or capholder assembly 404, with respect to the plunger assembly 12′.

In yet another preferred form of the invention, the cap holder 402, thecap holder assembly 404 or the plunger assembly 12′ will have astructure, element or the like that resists the relative axial movementof these parts when the cap holder 402 or the cap holder assembly 404 ispositioned fully within the plunger assembly 12′. In one preferred formof the invention the cap holder 402 has an annular protuberance 440 thatis dimensioned to fit within an annular groove 442 on the inner wallsurface 414 of the cap holder and preferably extends in line with thebase portions of the plunger ribs 434. A second locking structure isprovided having a plurality of teeth 450 which extend axially outwardfrom the outer wall surface 414 of the cap holder and are positioned inslots 424. In a preferred form of the invention the teeth extend axiallyoutwardly to a height beyond the height of the ribs 434. The teeth 450can be positioned in one or more of the slots or in each of the slots424 or in alternating slots or, as is shown, circumferentially spaced90° from one another. The teeth 450 preferably are positioned at anintermediate portion, between the base and the apex, of a slot 424. Theteeth 450 are dimensioned to fit within a segmented annular groove 452that extends circumferentially about the inner surface 412 crossingthrough the plunger ribs 434 at an intermediate portion, between thebase and the apex, of the plunger ribs 434.

FIGS. 56 a, b, c respectively show the assembly 400 in a ready-for-useposition, docked position, and used position. The assembly 400 is usedin essentially the same fashion as described above with respect to FIGS.3 and 4 except that when the assembly 400 is in the used position thecap holder 402 remains in the plunger assembly 12′.

The syringe barrel and plunger can be fabricated from any materialsuitable for its purpose and includes glass and polymeric material.Suitable polymeric materials include, but are not limited to,homopolymers, copolymers and terpolymers formed from monomers such asolefins, cyclic olefins, amides, esters, and ethers. The polymericmaterial may be a blend of more than one polymeric material and can be amonolayer structure or a multilayer structure. In one preferred form ofthe invention the syringe barrel and the plunger are injection moldedfrom a polypropylene material.

FIGS. 59-61 show a third embodiment 500 of an antiseptic cap equippedsyringe plunger and barrel assembly with the antiseptic cap assembly 80and lid stock 68 removed for clarity. The third embodiment 500 providesfor retrofitting an antiseptic cap assembly 502 to a standard plunger504. The antiseptic cap 502 has a first generally cylindrical outer wall506 having a proximal end 508 and a distal end 510. The proximal end 508is removably or fixedly attached to a button 512 of the plunger 504. Theproximal end has an opening 514 dimensioned to fit about the button 512and has a member for attaching to the button. In one preferred form ofthe invention, the attaching member includes a plurality ofcircumferentially spaced, and axially inwardly directed tabs 516extending from an inner wall surface 518 and the tabs engage a lowersurface of the button 512 to attach the antiseptic cap assembly 502 tothe plunger 504.

The distal end of the antiseptic cap 502 has a top annular flange 520extending radially inwardly from the first cylindrical wall 506 anddefines a generally circular opening 522. A second cylindrical wall 524extends axially downwardly from the top annular flange 520 and iscoaxially disposed within the first cylindrical wall 506. When theantiseptic cap 502 is attached to the plunger button 512 a bottomperipheral edge of the second cylindrical wall 524 will abut a topsurface of the plunger button 512 thereby capturing, by oppositelydirected axially forces, the plunger button 512 between the tabs 516 andthe second cylindrical wall. It is contemplated, however, that a secondset of tabs could be provided spaced axially away from the first set oftabs and the piston button 512 could be trapped between the two sets oftabs. Further, it is contemplated other attaching means could be usedthat are well known in the art and the attaching member shown is merelyexemplary.

The second cylindrical wall 524 defines a chamber as is shown in greaterdetail in FIG. 5 above with the ribs and slots as described for engagingthe antiseptic cap assembly 80 to prevent relative rotational movementand to resist relative axial movement of the parts when the antisepticcap assembly 80 is fully inserted into the chamber. Further, it iscontemplated adapting the plunger and syringe as described above toprevent or resist the relative rotational movement of the plunger withrespect to the barrel.

The piston 50 can be formed from any suitable material including apolymeric material or a silicone material. The stopper can be selectedfrom a material with a desired durometer so that reflux is reduced whenthe stopper engages an inner surface of the distal end wall of thesyringe barrel.

FIGS. 62-65 show a strip package 600 having a plurality of antisepticcap holder assemblies 602, attached to a single cover, or strip 604.Each of the cap holder assemblies 602 includes a cap holder 602 a and anantiseptic cap 602 b. The antiseptic cap 602 b could be any capdiscussed herein, such as the antiseptic cap 300 (FIG. 39) with a threadcover 302. Any number of disinfectant filled devices as discussedherein, such as the antiseptic cap holder assemblies 602, can beattached to one common cover or strip 604 of non-permeable (or very lowpermeable) film or foil laminate. The cover or strip 604 can be sealedto the holder 602 a of each disinfectant cap 602 b, or it could includea double seal, with one seal 606 between the strip 604 and the holder602 a, and another seal 608 between the strip 604 and the cap 602 b,e.g., sealed to the thread cover. The seal(s) could be between the strip604 and the holder 602 a. The double seal can provide an extra barrierto keep the disinfectant from evaporating from the cap 602 b whichprovides improved shelf life. Each device still remains individuallysterile, but a plurality of devices is chained to one another forconvenience through the use of the common strip 604. The strip package600 can include one or more holes, such as a die cut hole or holes, or ahanger 610 for hanging the strip 604 of product on a convenient hangersuch as an IV pole. The strip 604 may have notches and/or perforationsand/or scores that allow the user to tear an individual unit off forfuture use and still retain the individual sterile barrier of the unit.

The strip 604 could be thermally bonded to the holder 602 a and/or thecap 602 b using standard heat sealing technology, such as impulse,induction, conduction, radiant, or other heat sealing techniques.Alternatively, the strip 604 could be attached to the holder 602 aand/or the cap 602 b utilizing an adhesive bond or by a suitablemechanical or friction connection, such as a snap-fit. The caps 602 bare peelable from the strip 604 such that the peel force is less thanthe strength of the hanger 610. The peel force could generally be lessthan two pounds of force to start peeling, and less than one pound offorce to continue peeling. The strip 604 could be made of any suitablematerial, such as foil, plastic, a laminate, etc. In one aspect, thestrip 604 could be made of a foil material having a thickness ofapproximately 1 to 2 mil. The strip 604 could have a thick foil with atop coat of PET (polyethylene terephthalate), such as 48-gauge PET, thena polymer coat such as PDX which could be white, and a bottom coat of apeelable sealing layer, such as Allegro B, manufactured by RollprintPackaging Products, Inc. The sealing layer could form an adhesive bondthat could be peelable. The caps 602 b could be attached to the strip604 by induction heating of the foil, which melts the peelable sealinglayer to adhere it to the caps 602 b.

The holder 602 a prevents contamination of the cap 602 b when handled byvirtue of the flange of the holder 602 a which extends out from theholder 602 a and acts as a guard against contact of the top of the cap602 b by an user.

Suitable locking and flush solutions include a lower alcohol selectedfrom ethanol, propanol and butanol. The locking solution can be a singlelower alcohol or a blend of lower alcohols.

Suitable locking solutions can also include a lower alcohol with anantimicrobial and/or an anticoagulant. Suitable locking solutions cancontain at least one lower alcohol in a range from 1% to 99% by volumeand at least one other anti-microbial and/or anti-coagulant compound ina range from 1% to 99% by volume. The lower alcohol will usually be inaqueous solution, typically at 1% to 99% by volume, usually from 5% to95% by volume. The at least one other anti-microbial is selected fromthe group consisting of taurolidine and triclosan, and the at least oneanti-coagulant is selected from the group consisting of riboflavin,sodium citrate, ethylene diamine tetraacetic acid, and citric acid.

In one preferred form of the invention, the syringe assembly 10 will bepre-filled with one of the locking solutions and will be packaged by amanufacture and shipped to a health care provider. A cannula or needlewill be attached to the distal end of the barrel and placed into fluidcommunication with the fluid access site of an indwelling central venouscatheter. The flush solution will be injected into the catheter to cleanor lock the catheter. Afterwards, the cap assembly 80 will be removedfrom the plunger 17 and the cap will be docked to the fluid access siteof the catheter.

Citrate Salt Containing Antiseptic Solutions

In one form, the antiseptic is a solution a citrate salt and in anotherform of the invention the citrate salt solution is a hypertonicsolution. The term hypertonic is used herein to refer to a fluid havingan osmotic concentration and a density greater than the osmoticconcentration and density of the blood of the patient. The antisepticsolution preferably comprises a citrate salt with a concentration range,in weight percent, of from about 1.5% to about 50% with an osmolality ofabout 300 to about 6400 mOsm. More preferably, the antiseptic solutioncomprises citrate salt in a concentration range of from about 10% toabout 40%, yet more preferably, in a concentration range of from about20% to about 30%.

In a preferred embodiment, the antiseptic solution is prepared to have apH lower than that of the pH of the patient's blood. The citrate saltsolution may be prepared to have a pH lower than about 6.5, morepreferably, from about 4.5 to about 6.5. Also, the citrate salt solutioncan include pharmaceutically acceptable agents such as sodium chlorideand sodium heparin. The citrate salt solution can also include a varietyof other antibacterial, antimicrobial and anticoagulant agents such asgentamicin, vancomycin, and mixtures of these agents. Additionalanticoagulant agents include, for example heparin, urokinase, tissueplasminogen activation (tPA) and mixtures of these agents.

By “pharmaceutically acceptable,” it is meant that the citrate saltsolution and the included salts and other additives which are, withinthe scope of sound medical judgment, suitable for use in contact withtissues of humans and lower animals without undue toxicity, irritation,and allergic response. It is also typically necessary that a compositionbe sterilized to reduce the risk of infection.

Antibacterial Agent Containing Antiseptic Solutions

An antimicrobial agent containing antiseptic solution of the presentinvention may contain at least one alcohol, at least one antimicrobialagent and at least one chelator and/or anticoagulant. Variousantimicrobial substances as disclosed herein and that are well known toone of ordinary skill in the art may be combined with the lockingsolution in order to inhibit infection. The antimicrobial lockingsolution of the present invention may be use for filling or flushing amedical device such as an indwelling device such as an implantedcatheter. Other medical devices that are contemplated for use in thepresent invention are disclosed herein.

In another preferred form of the invention, the antiseptic agent cancontain antibacterial agents such as those classified asaminoglycosides, beta lactams, quinolones or fluoroquinolones,macrolides, sulfonamides, sulfamethoxazoles, tetracyclines,streptogramins, oxazolidinones (such as linezolid), clindamycins,lincomycins, rifamycins, glycopeptides, polymyxins, lipo-peptideantibiotics, as well as pharmacologically acceptable sodium salts,pharmacologically acceptable calcium salts, pharmacologically acceptablepotassium salts, lipid formulations, derivatives and/or analogs of theabove.

The aminoglycosides are bactericidal antibiotics that bind to the 30Sribosome and inhibit bacterial protein synthesis. They are typicallyactive against aerobic gram-negative bacilli and staphylococci.Exemplary aminoglycosides that may be used in some specific aspects ofthe invention include amikacin, kanamycin, gentamicin, tobramycin, ornetilmicin.

Suitable beta lactams are selected from a class of antibacterials thatinhibit bacterial cell wall synthesis. A majority of the clinicallyuseful beta-lactams belong to either the penicillin group (penam) orcephalosporin (cephem) groups. The beta-lactams also include thecarbapenems (e.g., imipenem), and monobactams (e.g., aztreonam).Inhibitors of beta-lactamase such as clavulanic acid and its derivativesare also included in this category.

Non-limiting examples of the penicillin group of antibiotics that may beused in the solutions of the present invention include amoxicillin,ampicillin, benzathine penicillin G, carbenicillin, cloxacillin,dicloxacillin, piperacillin, or ticarcillin, etc. Examples ofcephalosporins include ceftiofur, ceftiofur sodium, cefazolin, cefaclor,ceftibuten, ceftizoxime, cefoperazone, cefuroxime, cefprozil,ceftazidime, cefotaxime, cefadroxil, cephalexin, cefamandole, cefepime,cefdinir, ceftriaxone, cefixime, cefpodoximeproxetil, cephapirin,cefoxitin, cefotetan etc. Other examples of beta lactams includeimipenem or meropenem which are extremely active parenteral antibioticswith a spectrum against almost all gram-positive and gram-negativeorganisms, both aerobic and anaerobic and to which Enterococci, B.fragilis, and P. aeruginosa are particularly susceptible.

Suitable beta lactamase inhibitors include clavulanate, sulbactam, ortazobactam. In some aspects of the present invention, the antibacterialsolutions may comprise a combination of at least one beta lactam and atleast one beta lactamase inhibitor.

Macrolide antibiotics are another class of bacteriostatic agents thatbind to the SOS subunit of ribosomes and inhibit bacterial proteinsynthesis. These drugs are active against aerobic and anaerobicgram-positive cocci, with the exception of enterococci, and againstgramnegative anaerobes. Exemplary macrolides include erythromycin,azithromycin, clarithromycin.

Quinolones and fluoroquinolones typically function by their ability toinhibit the activity of DNA gyrase. Examples include nalidixic acid,cinoxacin, trovafloxacin, ofloxacin, levofloxacin, grepafloxacin,trovafloxacin, sparfloxacin, norfloxacin, ciprofloxacin, moxifloxacinand gatifloxacin.

Sulphonamides are synthetic bacteriostatic antibiotics with a widespectrum against most gram-positive and many gram-negative organisms.These drugs inhibit multiplication of bacteria by acting as competitiveinhibitors of p-aminobenzoic acid in the folic acid metabolism cycle.Examples include mafenide, sulfisoxazole, sulfamethoxazole, andsulfadiazine.

The tetracycline group of antibiotics include tetracycline derivativessuch as tigecycline which is an investigational new drug (IND),minocycline, doxycycline or demeclocycline and analogs such asanhydrotetracycline, chlorotetracycline, or epioxytetracycline.

Suitable streptogramin class of antibacterial agents includequinupristin, dalfopristin or the combination of two streptogramins.

Drugs of the rifamycin class typically inhibit DNA-dependent RNApolymerase, leading to suppression of RNA synthesis and have a verybroad spectrum of activity against most grampositive and gram-negativebacteria including Pseudomonas aeruginosa and Mycobacterium species. Anexemplary rifamycin is rifampicin.

Other antibacterial drugs are glycopeptides such as vancomycm,teicoplanin and derivatives thereof. Yet other antibacterial drugs arethe polymyxins which are exemplified by colistin.

In addition to these several other antibacterial agents such aspristinamycin, chloramphenicol, trimethoprim, fusidic acid,metronidazole, bacitracin, spectinomycin, nitrofurantoin, daptomycin orother lipopeptides, oritavancin, dalbavancin, ramoplanin, ketolide etc.may be used in preparing the antiseptic solutions described herein. Ofthese, metronidazole is active only against protozoa, such as Giardialamblia, Entamoeba histolytica and Trichomonas vaginalis, and strictlyanaerobic bacteria. Spectinomycin, is a bacteriostatic antibiotic thatbinds to the 30S subunit of the ribosome, thus inhibiting bacterialprotein synthesis and nitrofurantoin is used orally for the treatment orprophylaxis of UTI as it is active against Escherichia coli,Klebsiella-Enterobacter species, staphylococci, and enterococci.

In other embodiments, the antimicrobial agent is an antifungal agent.Some exemplary classes of antifungal agents include imidazoles ortriazoles such as clotrimazole, miconazole, ketoconazole, econazole,butoconazole, omoconazole, oxiconazole, terconazole, itraconazole,fluconazole, voriconazole, posaconazole, ravuconazole or flutrimazole;the polyene antifungals such as amphotericin B, liposomal amphotericinB, natamycin, nystatin and nystatin lipid formulations; the cell wallactive cyclic lipopeptide antifungals, including the echinocandins suchas caspofungin, micafungin, anidulafungin, cilofungin; LY121019;LY303366; the allylamine group of antifungals such as terbinafine. Yetother non-limiting examples of antifungal agents include naftifine,tolnaftate, mediocidin, candicidin, trichomycin, hamycin, aureofungin,ascosin, alfattni, azacolutin, trichomycin, levorin, heptamycin,calcimycin, griseofulvin, BF-796, MTCH 24, BTG-137586, pradimicins (MNS18184), benanomicin; ambisome; nikkomycin Z; flucytosine, or perimycin.

In another preferred form of the invention, the antimicrobial agent isan antiviral agent. Non-limiting examples of antiviral agents includecidofovir, amantadine, rimantadine, acyclovir, gancyclovir, pencyclovir,famciclovir, foscarnet, ribavirin, or valacyclovir. In some forms of theinvention the antimicrobial agent is an innate immune peptide orproteins. Some exemplary classes of innate peptides or proteins aretransferrins, lactoferrins, defensins, phospholipases, lysozyme,cathelicidins, serprocidins, bactericidal permeability mcreasmgproteins, amphipathic alpha helical peptides, and other syntheticantimicrobial proteins.

In other embodiments of the invention, the antimicrobial agent is anantiseptic agent. Several antiseptic agents are known in the art andthese include a taurinamide derivative, a phenol, a quaternary ammomumsurfactant, a chlorine-containing agent, a quinaldinium, a lactone, adye, a thiosemicarbazone, a quinone, a carbamate, urea, salicylamide,carbanilide, a guanide, an amidine, an imidazoline biocide, acetic acid,benzoic acid, sorbic acid, propionic acid, boric acid, dehydroaceticacid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid,isopropanol, propylene glycol, benzyl alcohol, chlorobutanol,phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde,glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodiumhypochlorite, iodine (in vanous solvents), povidone-iodine,hexamethylenetetramine, noxythiolin, 1-(3-chloroallyl)-3,5,7-triazo1-azoniaadamantane chloride, taurolidine, taurultam,N(5-nitro-2-furfurylidene)-1-aminohydantoin, 5-nitro-2-furaldehydesemicarbazone, 3,4,4′-trichlorocarbanilide,3,4′,5-tribromosalicylanilide,3-trifluoromethyl-4,4′-dichlorocarbanilide, 8-hydroxyquinoline,1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid,1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene,parachlorometaxylenol, 2,4,4′-trichloro-2′-hydroxydiphenol, thymol,chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silversulfadiazine, or silver nitrate.

In another preferred form of the invention, the antiseptic solutionincludes a basic reagent and a dye. The basic reagent may be a guanidiumcompound, a biguanide, a bipyridine, a phenoxide antiseptic, an alkyloxide, an aryl oxide, a thiol, a halide, an aliphatic amine, or anaromatic amine. In some specific aspects, the basic reagent is aguanidium compound. Nonlimiting examples of guanidium compounds includechlorhexidine, alexidine, hexamidine. In other specific embodiments, thebasic reagent is a bipyridine. One example of a bipyridine isoctenidine. In yet other aspects, the basic reagent is a phenoxideantiseptic.

The dye may be a triarylmethane dye, a monoazo dye, a diazo dye, anindigoid dye, a xanthene dye, an anthraquinone dye, a quinoline dye, anFD&C dye. Non-limiting examples of triarylmethane dye include gentianviolet, crystal violet, ethyl violet, or brilliant green. Exemplarymonoazo dyes include FD&C Yellow No. 5, or FD&C Yellow No. 6. Othernonlimiting examples of FD&C dye include Blue No. 1 or Green No. 3. Onenon-limiting example of diazo dyes is D&C Red No. 17. An example of anindigoid dye is FD&C Blue No. 2. An example of a xanthene dye is FD&CRed No. 3; of an anthraquinone dye is D&C Green No. 6; and of anquinoline dye is D&C Yellow No. 1.

Other examples of antiseptics that may be used to the solutions of theinvention are the phenoxide antiseptics such as clofoctol, chloroxylenolor triclosan. Still other antiseptic agents that may be used to preparethe antimicrobial solutions of the invention are gendine, genlenol,genlosan, or genfoctol.

One of skill in the art will appreciate that one can use one or more ofthe antimicrobial agents including one or more antibacterial agent,and/or one or more antifungal agent, and/or one or more antiviral agent,and/or one or more antiseptic agent, and/or combinations thereof.

A wide variety of chelator agents are contemplated as useful inpreparing the antiseptic solutions of the invention. This includeschelators such as EDT A free acid, EDTA 2N a, EDT A. 3Na, EDTA 4Na, EDTA2K, EDTA 2Li, EDTA 2NH4, EDTA 3K, Ba(Il)-EDTA, Ca(Il)-EDTA,Co(Il)-EDTACu(Il)-EDTA, Dy(III)-EDT A, Eu(IIl)-EDT A, Fe(IIl)-EDT A,In(III-EDT A, La(III)-EDTA, CyDTA, DHEG, diethylenetriamine penta aceticacid (DTPA), DTPA-OH, EDDA, EDDP, EDDPO, EDTA-OH, EDTPO, EGTA, HBED,HDTA, HIDA, IDA, MethylEDTA, NTA, NTP, NTPO, 0-Bistren, TTHA, EGTA,DMSA, deferoxamine, dimercaprol, zinc citrate, a combination of bismuthand citrate, penicillamine, succimer or Etidronate. It is contemplatedthat any chelator which binds barium, calcium, cerium, cobalt, copper,iron, magnesium, manganese, nickel, strontium, or zinc will beacceptable for use in the present invention.

Alternatively, one may use at least one anticoagulant such as heparin,hirudin, EGTA, EDTA, urokinase, streptokinase, hydrogen peroxide etc.,in the preparation of the antimicrobial solutions of the invention.

In addition to the alcohols set forth above, a variety of alcohols arecontemplated as useful in the preparation of the instant antisepticsolution, and include any antimicrobially active alcohol. Non-limitingexamples of alcohols include ethanol, methanol, isopropanol, propyleneglycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, and thelike.

One of skill in the art will appreciate that the solutions of theinstant invention can comprise various combinations of at least onealcohol, at least one antimicrobial agent, and at least onechelator/anticoagulant. In some specific embodiments, the solution ofthe invention comprises at least one alcohol, at least one tetracyclineand at least one chelator/anticoagulant. In a specific aspect, such anantimicrobial solution comprises ethanol, at least one tetracycline andEDTA or heparin.

In other specific aspects, such a solution comprises ethanol,minocycline and EDTA or heparin. In one embodiment of this aspect, theconcentration of minocycline is 0.001 mg/ml to 100 mg/ml. In anotherembodiment, the concentration of minocycline is about 3 mg/ml. Inanother aspect, the concentration of EDT A is in the range of 10-100mg/ml. In one embodiment of this aspect, the concentration of EDTA isabout 30 mg/ml.

In another preferred form of the invention, the antiseptic solutionincludes a pharmacologically acceptable sodium salt, a pharmacologicallyacceptable calcium salt, a pharmacologically acceptable potassium saltand about one milligram per milliliter polyhexamethylene biguanidehydrochloride in an aqueous admixture. Additionally, the solution of theinvention may also contain a pharmacologically acceptable salt of lacticacid.

Salt Containing Antiseptic Solutions

One preferred antiseptic solution includes a pharmacologicallyacceptable sodium salt such as sodium chloride or the like in aconcentration of between about 820 mg to about 900 mg, apharmacologically acceptable calcium salt, such as calcium chloridedihydrate or the like in a concentration between about 30.0 mg to about36.0 mg, a pharmacologically acceptable potassium salt, such aspotassium chloride or the like in a concentration between about 28.5 toabout 31.5 mg and about one milligram per milliliter polyhexamethylenebiguanide hydrochloride in an aqueous admixture with one hundredmilliliters of water for injection U.S.P. For particular applications,the solution of the invention may also include sodium lactate in aconcentration between about 290 mg and about 330 mg in the one hundredmilliliter aqueous admixture.

Photo-Oxidant Solutions

In another preferred form of the present invention, the antisepticsolution contains an anticoagulant and a photo-oxidant. In certainembodiments, a photo-oxidant is selected that has an antiseptic effect.As used herein, the term “photo-oxidant” is intended to refer to acompound (usually an organic dye) that has photo-oxidation properties,in which the compound exhibits an increased oxidizing potential uponexposure to radiant energy such as light. The term “photooxidant” alsorefers to a composition that releases one or more electrons when struckby light.

In one preferred aspect of the invention, the photo-oxidant is methyleneblue, which advantageously provides antibiotic and antifungal activity,and also provides a color to make the antiseptic solution clearlyidentifiable. In addition to methylene blue, other photo-oxidants mayinclude Rose Bengal, hypericin, methylene violet, proflavine, rivanol,acriflavine, toluidine blue, trypan blue, neutral red, a variety ofother dyes or mixtures thereof. Therefore, in alternate aspects of theinvention, one or more alternative photo-oxidants, preferably a coloredphotooxidant is used in accordance with the invention in place ofmethylene blue.

Enhanced Viscosity Solutions

In another preferred form of the invention, the antiseptic solutionincludes a low viscosity antibacterial agent mixed with a viscosityincreasing agent. Examples of antibacterial agents which may be used, inaddition to those described above, comprise alcohols, chlorhexidine,Chlorpactin, iodine, taurolidine, citric acid, and soluble citric acidsalts, particularly sodium citrate, optionally mixed with water.

Suitable viscosity increasing agents include Carbopol, starch,methylcellulose, carboxypolymethylene, carboxymethyl cellulose,hydroxypropylcellulose, or the like. Carbopol is a cross-linkedpolyacrylic acid based polymer sold by Noveon, Inc. It is preferablyneutralized to about pH 7 with a base material such astetrahydroxypropyl ethylene diamine, triethanolamine, or sodiumhydroxide. Derivatives of starch may also be used, such ashydroxyethylstarch, hydroxypropylstarch, or starch having bonded organicacid ester groups, to improve compatibility with antibacterial agentssuch as alcohols, for example, ethanol or isopropanol. Such ester groupsmay be the reaction product of two to twelve carbon organic acids withthe starch, for example. Also, the elevated viscosity antisepticsolution may be created by the use of a fat emulsion, or otherdispersions in water/alcohol of glycerol mono or di esters of fattyacids, or fatty acid esters of other polyols such as sugars having oneor more bonded fatty acid groups per molecule. Analogous compounds withether linkages may also be used.

Also, other materials such as alginic acid, with or without calciumcitrate may be used, or polyvinyl alcohol, with or without borax,povidone, polyethylene glycol alginate, sodium alginate, and/ortragacanth. If desired, the fluid of this invention may also contain aneffective amount of an antithrombogenic agent such as heparin, and adiluent such as water, along with other desired ingredients.

In one preferred form of the invention, the antiseptic solution containsa mixture of isopropyl alcohol and neutralized Carbopol, with otheroptional ingredients being present such as water, antithrombogenicagents such as heparin, and the like. Preferably, about 0.4 to 2 weightpercent of Carbopol is present. Citric acid may also be present as anantibacterial agent, either with or as a substitute for anotheranti-bacterial agent such as isopropyl alcohol or ethanol.

In another embodiment, the antiseptic solution is a gel of an isopropylalcohol, optionally with up to about 30 weight percent water, and about2.2 weight percent hydroxypropylcellulose, to form a high viscosityantiseptic solution.

In yet another preferred form of the invention, the antiseptic solutioncontains carbohydrates and/or glucose degradation products. Suitablecarbohydrates are chosen form the group of glucose and/or fructose.Suitable degradation products include 3-deoxyglucosone (3-DG),acetaldehyde, formaldehyde, acetaldehyde, glyoxal, methylglyoxal,5-hydroxymethyl-2-furaldehyde (5-HMF), 2-furaldehyde, and3,4-dideoxyglucosone-3-ene (3,4-DGE).

Other suitable agents to be used in this embodiment of the antisepticsolution includes substances having anticoagulatory properties i.e.,inhibitors of the coagulation cascade such as heparin of standard andlow molecular weight, fractionated heparin, synthetic inhibitors in thecoagulation cascade, Futhan as a broad protease inhibitor, complexingand chelating substances such as citrate, EDTA, EGTA, substances andmixtures used for preservation of blood products (platelets or plasma),CDPA (citrate, sodium phosphate, dextrose, adenine), synthetic ornatural thrombin inhibitor substances. Other suitable additives includefucoidan, riboflavin, vitamin E, alphatocopherol, folic acid and aminoacids. Furthermore, antiinflammatory compounds and drugs could also beused, e.g. cortison, mycophenolic acid (MPA) and derivates thereof,sirolimus, tacrolimus and cyclosporin, diclofenac, etc.

Inhibitory peptides can also be used in the antiseptic solution such asdefensins, (dermcidin), and others. Radicals, such as reactive oxygenespecies, NO-releasing systems or nitric oxide (NO), and peroxynitritemay also be used. A buffer composition may also be included in theantiseptic solution, and in one preferred form of the invention, thebuffer contains lactate, bicarbonate, pyruvate, ethyl pyruvate andcitric acid in combination and mixtures including adjustment of pH byacetic acid, hydrochloric acid or sulphuric acid. Furthermore, viscosityenhancing additives may be added, such as lipids or lipidic substances(also to get water insoluble vitamins or complexes into solution),nutrients in high concentration density gradient e.g. aminoacidcontaining fluids, polyglucose, Icodextrin, pectin, hydroxyethyl starch(HES), alginate, hyaluronic acid, etc.

Taurolidine Antiseptic Solutions and Gels

The antiseptic solutions of the present invention can includeTaurolidine and/or Taurultam to prevent clotting and Biofilm formationor the elements can be combined with other antimicrobial agents. Oneembodiment of the present invention is a gel with thixotropic propertiesto keep the solution inside the antiseptic cap and not spill out duringthe time interval between uses. This is accomplished by making ahydrogel matrix as a drug delivery vehicle containing a biocompatibleantimicrobial agent alone or with another active agent, which may beuseful for particular purposes. The hydrogel matrix is biocompatibleand, biodegradable in the bloodstream. The matrix can be a hydrogel(e.g., pectin, gelatin, etc), a protein (e.g., collagen, hemoglobin,etc), a colloidal substance (e.g., serum albumin etc.), an emulsion orother adjuvant. Preferably, the matrix shall have structural integrityand be thixotropic. Thixotropy is a property, which is exhibited bycertain gels. It is a property characterized by a solid or semisolidsubstance that when shaken, stirred or subject to high shear forcesbecomes fluid like and can flow and then returns to the semisolid statewhen the forces and/movement are stopped. Alternatively, the gel couldhave the properties similar to that of the colloidal dispersion whichresists movement, or flow until a high shear force is imparted to thefluid and then it flows easily.

Other ingredients may be added to the gel matrix to provide furtherfunctional benefit. The preferred antimicrobial is Taurolidine, whichcan be added to the matrix as a micro particle powder, or encapsulatedin liposomes, microspheres, or nanospheres. It should be appreciatedthat numerous active agents and drugs can be added to the thixotropicgel including sterilants, lysing agents (such as Urokinase), imagingenhancers, catheter surface modifiers, antibiotics and antimicrobialchemicals.

A hydrogel comprises a three-dimensional molecular network containinglarge quantities of water giving them good biocompatibility withmaterial consistency that is soft solid-like with high diffusiveproperties to gases, chemicals and proteins. Suitable hydrogels includenatural polymers including serum albumin, collagen, or alginates,polyvinyl alcohol, poly (ethylene oxide) or poly (hydroxyethylene) andpolyelectrolytes, such as poly(acrylic acid), poly(styrene sulfonate),and carboxymethylcellulose (CMC).

One preferred form of the antiseptic solution includes Taurolidine withSalicylic acid or Sodium Salicylate in an aqueous solvent. SalicylicAcid and Sodium Salicylate are drugs that have been used with antibioticlocks in catheters to enhance the biocidal action of the antibioticalone and to inhibit the attachment of microbes to surfaces. This lastattribute is especially important because the initiation of a Biofilmexpression and growth require that the individual bacteria must firstattach themselves to the underlying surface. By stopping attachment,Biofilm formation is blocked.

Sodium salicylate has been demonstrated to have remarkable antibacterialactivity, including the ability to enhance the activities of certainantibiotics. This drug inhibits adherence, growth and Biofilm formation.

EDTA Containing Antiseptic Solutions

In one preferred antiseptic solution of the present invention providesantimicrobial, antifungal, anti-viral and anti-amoebic properties andmay also serve as an anti-coagulant. Specified salts and compositions ofethylene diamine tetraacetic acid (EDTA) (C₁₀H₁₂N₂Na₄O₈) are used atspecified concentrations and pH levels.

The EDTA formulations of the present invention are safe for humanadministration and are biocompatible and non-corrosive. They may alsohave anticoagulant properties and are thus useful for preventing and/ortreating a variety of catheter-related infections. In one embodiment,antiseptic solutions of the present invention have at least four, andpreferably at least five, of the following properties: anticoagulantproperties; inhibitory and/or bactericidal activity against a broadspectrum of bacteria in a planktonic form; inhibitory and/or fungicidalactivity against a spectrum of fungal pathogens; inhibitory and/orbactericidal activity against a broad spectrum of bacteria in a sessileform; inhibitory activity against protozoan infections; inhibitoryactivity against Acanthamoeba infections; safe and biocompatible, atleast in modest volumes, in contact with a patient; safe andbiocompatible, at least in modest volumes, in a patient's bloodstream;and safe and compatible with industrial objects and surfaces. Theantiseptic solution can have a pH higher than physiological pH such as apH of >8.0, or at a pH>8.5, or at a pH>9, or at a pH>9.5.

In another preferred form of the invention, the antiseptic solutioncontain a sodium EDTA salt (or combination of sodium salts) in solutionat a pH in the range between 8.5 and 12.5 and, in another embodiment, ata pH of between 9.5 and 11.5 and, in yet another embodiment, at a pH ofbetween 10.5 and 11.5.

When used herein, the term “EDTA salt” may refer to a single salt, suchas a di-sodium or tri-sodium or tetra-sodium salt, or another EDTA saltform, or it may refer to a combination of such salts. The composition ofEDTA salt(s) depends both on the EDTA salts used to formulate thecomposition, and on the pH of the composition. For antiseptic solutionsof the present invention consisting of sodium EDTA salt(s), and at thedesired pH ranges (specified above), the sodium EDTA salts arepredominantly present in both the tri-sodium and tetra-sodium saltforms.

In one embodiment, the antiseptic solution contains a combination of atleast the trisodium and tetra-sodium salts of EDTA, and more preferablysolutions containing at least 10% of the EDTA in the composition ispresent in the tetra-sodium salt form. In yet another embodiment, atleast 50% and, more preferably at least 60%, of the EDTA in thecomposition is present in the tri-sodium salt form.

EDTA solutions of the present invention are preferably provided in asterile and nonpyrogenic form and may be packaged in any convenientfashion. The compositions may be prepared under sterile, asepticconditions, or they may be sterilized following preparation and/orpackaging using any of a variety of suitable sterilization techniques.

Formulation and production of antiseptic compositions of the presentinvention is generally straightforward. In one embodiment, desiredantiseptic solutions of the present invention are formulated bydissolving one or more EDTA salt(s) in an aqueous solvent, such aspurified water, to the desired concentration and adjusting the pH of theEDTA salt solution to the desired pH. The antiseptic solution may thenbe sterilized using conventional means, such as autoclaving, UVirradiation, filtration and/or ultrafiltration, and other means. Thepreferred osmolarity range for EDTA solutions is from 240-500 mOsm/Kg,more preferably from 300-420 mOsm/Kg. The solutions are preferablyformulated using USP materials.

Antiseptic solutions containing sodium salts of EDTA other than tri- andtetra-sodium salts, such as di-sodium EDTA, is also contemplated. Forexample di-sodium EDTA solutions can be used but such solutions have alower pH in solution than the desired pH range of compositions of thepresent invention but, upon pH adjustment to the desired range using apH adjustment material, such as sodium hydroxide, sodium acetate, andother well-known pH adjustment agents, EDTA solutions prepared usingdi-sodium salts are converted to the preferred combination di- and/ortri- and/or tetra-sodium salt EDTA solutions of the present invention.Thus, different forms and combinations of EDTA salts may be used in thepreparation of EDTA compositions of the present invention, provided thatthe pH of the composition is adjusted to the desired pH range prior touse. In one embodiment, antiseptic compositions consisting of a mixtureof primarily tri- and tetra-sodium EDTA is provided by dissolvingdi-sodium EDTA in an aqueous solution, 3%-5% on a weight/volume basis,and adding sodium hydroxide m a volume and/or concentration sufficientto provide the desired pH of >8.5 and <12.0.

Antibacterial Enzyme Containing Antiseptic Solutions

“Antibacterial enzyme” refers to any proteolytic, pore-forming,degradative or inhibitory enzyme that kills or damages a bacterialspecies or particular strain thereof. The result may be achieved bydamaging the cell wall of the bacteria, disrupting cell membranesassociated with the cell wall or within the bacteria, inhibiting proteinsynthesis within the bacteria, disrupting the sugar backbone, or by anyother mechanism attributed to a peptide or protein considered by thoseskilled in the art to be an antibacterial enzyme. The enzyme may be anatural, wild-type enzyme, modified by conventional techniques,conjugated to other molecules, recombinantly expressed, or syntheticallyconstructed.

One example of an antibacterial enzyme is lysostaphin. Lysostaphin isimportant because it is effective in the treatment of staphylococci andbiofilms formed therefrom. “Lysostaphin,” and “lysostaphin analogues”are defined as including lysostaphin (wild type), any lysostaphin mutantor variant, any recombinant, or related enzyme (analogue) or anysynthetic version or fragment of lysostaphin (whether synthetic orotherwise) that retains the proteolytic ability, in vivo and in vitro,to cleave the cross-linked polyglycine bridges in the cell wallpeptidoglycan of staphylococci. The enzymes may be generated bypost-translational processing of the protein (either by enzymes presentin a producer strain or by means of enzymes or reagents introduced atany stage of the process) or by mutation of the structural gene.Mutations may include site deletion, insertion, domain removal andreplacement mutations.

The lysostaphin may be synthetically constructed, expressed in mammaliancells, insects, bacteria, yeast, reptiles or fungi, recombinantlyexpressed from a cell culture or higher recombinant species such as amouse, or otherwise. This would include the activity-retaining syntheticconstruction including synthetic peptides and polypeptides orrecombinant expression of portions of the lysostaphin enzyme responsiblefor its activity against staphylococci as part of a larger protein orpeptide, include chimeric proteins, containing the active sites of oneor more other antibacterial enzymes that are effective either againststaphylococci or other biofilmforming bacteria species.

The antibacterial enzymes may also be coated on the surface of thedevices described herein by immersion of the device in a solution of theenzyme for a length of time sufficient to form a biofilm-formationinhibiting coating of the enzyme on the susceptible surface. Even themost minimal concentration of enzyme will confer some protection.Typically, a concentration of from about 10 μg/ml to about 100 mg/ml canbe used. With device surfaces, the coatings may also be formed bycovalent attachment of the enzyme thereto.

Antiseptic Coatings

It is contemplated that the devices described herein can be coated withan antiseptic coating by any suitable technique such as immersion of thepart into an antiseptic solution, by spray coating the part with theantiseptic solution, by blending the antiseptic solution or materialinto the polymeric material used to fabricate the device.

In one preferred form of the invention, a quantity of physiological,antimicrobial metal compound is added to the resin for direct molding ofan article. Physiological, antimicrobial metals are meant to include theprecious metals, such as silver, gold and platinum, and copper and zinc.Physiological, antimicrobial metal compounds used herein include oxidesand salts of preferably silver and also gold, for example: silveracetate, silver benzoate, silver carbonate, silver citrate, silverchloride, silver iodide, silver nitrate, silver oxide, silver sulfadiazine, silver sulfate, gold chloride and gold oxide. Platinumcompounds such as chloroplatinic acid or its salts (e.g., sodium andcalcium chloroplatinate) may also be used. Also, compounds of copper andzinc may be used, for example: oxides and salts of copper and zinc suchas those indicated above for silver. Single physiological, antimicrobialmetal compounds or combinations of physiological, antimicrobial metalcompounds may be used.

Preferred physiological, antimicrobial metal compounds used in thisinvention are silver acetate, silver oxide, silver sulfate, goldchloride and a combination of silver oxide and gold chloride. Theparticles of the silver compounds are sufficiently able to be extractedto form a zone of inhibition to prevent and kill bacteria growth.

In another preferred form of the invention the devices herein areimpregnated with triclosan and silver compounds or triclosan andchlorhexidine.

It is to be understood that the foregoing description is not intended tolimit the spirit or scope of the disclosure. It will be understood thatthe aspects of the disclosure described herein are merely exemplary andthat a person skilled in the art may make many variations andmodification without departing from the spirit and scope of thedisclosure. All such variations and modifications, including thosediscussed above, are intended to be included within the scope of thedisclosure.

What is claimed is:
 1. A strip package for carrying at least two capassemblies configured to disinfect one or more access sites, the strippackage comprising: at least two cap assemblies, each of the at leasttwo cap assemblies comprising: a cap holder comprising a holder outerwall and a holder inner surface forming a chamber, the chamber having anopen end and a closed end, and an antiseptic cap configured to bepositioned within the chamber of the cap holder, the antiseptic capcomprising a sidewall forming a cap chamber and an antiseptic substancewithin the cap chamber; and a strip extending over and forming a sealwith each of the cap holders of each of the at least two cap assemblies,the strip comprising a perforation configured to allow a user toindividually separate one or more of the at least two cap assembliesfrom the strip package along the perforation such that the seal witheach of the one or more separated cap assemblies is maintained, whereineach of the antiseptic caps further comprises a plurality ofcircumferentially spaced cap ribs on a cap external surface, and whereinthe plurality of circumferentially spaced cap ribs extend radiallyoutwardly from and axially along the sidewall.
 2. The strip package ofclaim 1, wherein the strip includes a hole.
 3. The strip package ofclaim 1, wherein each of the seals comprises a thermal bond.
 4. Thestrip package of claim 1, wherein each of the seals comprises anadhesive bond.
 5. The strip package of claim 1, wherein each of theseals comprises a mechanical connection.
 6. The strip package of claim1, wherein each of the seals comprises a snap-fit.
 7. The strip packageof claim 1, wherein the strip comprises foil.
 8. The strip package ofclaim 1, wherein a peel force capable of removing each of the at leasttwo cap assemblies from the strip is less than two pounds of force. 9.The strip package of claim 1, wherein each of the cap holders furthercomprises a plurality of circumferentially spaced holder ribs on theholder inner surface, and wherein the plurality of circumferentiallyspaced holder ribs are configured to engage the plurality ofcircumferentially spaced cap ribs.
 10. The strip package of claim 1,wherein the antiseptic substance comprises a liquid, and wherein theliquid is releasably retained within an absorbent material positionedwithin each of the cap chambers.
 11. The strip package of claim 1,wherein the antiseptic substance comprises a coating on at least aportion of the sidewall of each of the antiseptic caps.
 12. The strippackage of claim 1, wherein each of the antiseptic caps furthercomprises a set of threads on a cap inner surface.
 13. The strip packageof claim 1, wherein each of the cap holders comprises a holder flange.14. The strip package of claim 1, wherein the strip forms a second sealwith each of the at least two cap assemblies.
 15. The strip package ofclaim 14, wherein the strip forms the second seal between the strip andeach of the caps of each of the at least two cap assemblies.
 16. Thestrip package of claim 15, wherein each of said second seals is arrangedsubstantially concentric with respect to each of said respective seals.17. The strip package of claim 14, wherein the strip comprises anunsealed portion located between the seal and the second seal.
 18. Thestrip package of claim 1, wherein the at least two cap assemblies arearranged in a single row.
 19. A strip package for carrying at least twocap assemblies configured to disinfect one or more access sites, thestrip package comprising: at least two cap assemblies, each of the atleast two cap assemblies comprising: a cap holder comprising a holderouter wall and a holder inner surface forming a chamber, the chamberhaving an open end and a closed end, and an antiseptic cap configured tobe positioned within the chamber of the cap holder, the antiseptic capcomprising a sidewall forming a cap chamber and an antiseptic substancewithin the cap chamber; and a strip extending over and forming a sealwith each of the cap holders of each of the at least two cap assemblies,the strip comprising a perforation configured to allow a user toindividually separate one or more of the at least two cap assembliesfrom the strip package along the perforation such that the seal witheach of the one or more separated cap assemblies is maintained, whereinthe antiseptic substance comprises a liquid, and wherein the liquid isreleasably retained within an absorbent material positioned within eachof the cap chambers.
 20. The strip package of claim 19, wherein thestrip includes a hole.
 21. The strip package of claim 19, wherein eachof the seals comprises a thermal bond.
 22. The strip package of claim19, wherein each of the seals comprises an adhesive bond.
 23. The strippackage of claim 19, wherein each of the seals comprises a mechanicalconnection.
 24. The strip package of claim 19, wherein each of the sealscomprises a snap-fit.
 25. The strip package of claim 19, wherein thestrip comprises foil.
 26. The strip package of claim 19, wherein a peelforce capable of removing each of the at least two cap assemblies fromthe strip is less than two pounds of force.
 27. The strip package ofclaim 19, wherein the antiseptic substance comprises a coating on atleast a portion of the sidewall of each of the antiseptic caps.
 28. Thestrip package of claim 19, wherein each of the antiseptic caps furthercomprises a set of threads on a cap inner surface.
 29. The strip packageof claim 19, wherein each of the cap holders comprises a holder flange.30. The strip package of claim 19, wherein the strip forms a second sealwith each of the at least two cap assemblies.
 31. The strip package ofclaim 30, wherein the strip forms the second seal between the strip andeach of the caps of each of the at least two cap assemblies.
 32. Thestrip package of claim 31, wherein each of said second seals is arrangedsubstantially concentric with respect to each of said respective seals.33. The strip package of claim 30, wherein the strip comprises anunsealed portion located between the seal and the second seal.
 34. Thestrip package of claim 19, wherein the at least two cap assemblies arearranged in a single row.
 35. A strip package for carrying at least twocap assemblies configured to disinfect one or more access sites, thestrip package comprising: at least two cap assemblies, each of the atleast two cap assemblies comprising: a cap holder comprising a holderouter wall and a holder inner surface forming a chamber, the chamberhaving an open end and a closed end, and an antiseptic cap configured tobe positioned within the chamber of the cap holder, the antiseptic capcomprising a sidewall forming a cap chamber and an antiseptic substancewithin the cap chamber; and a strip extending over and forming a sealwith each of the cap holders of each of the at least two cap assemblies,the strip comprising a perforation configured to allow a user toindividually separate one or more of the at least two cap assembliesfrom the strip package along the perforation such that the seal witheach of the one or more separated cap assemblies is maintained whereineach of the seals comprises a snap-fit.
 36. The strip package of claim35, wherein a peel force capable of removing each of the at least twocap assemblies from the strip is less than two pounds of force.
 37. Thestrip package of claim 35, wherein the strip forms a second seal witheach of the at least two cap assemblies.
 38. The strip package of claim37, wherein the strip forms the second seal between the strip and eachof the caps of each of the at least two cap assemblies.
 39. The strippackage of claim 38, wherein each of said second seals is arrangedsubstantially concentric with respect to each of said respective seals.40. The strip package of claim 37, wherein the strip comprises anunsealed portion located between the seal and the second seal.
 41. Astrip package for carrying at least two cap assemblies configured todisinfect one or more access sites, the strip package comprising: atleast two cap assemblies, each of the at least two cap assembliescomprising: a cap holder comprising a holder outer wall and a holderinner surface forming a chamber, the chamber having an open end and aclosed end, and an antiseptic cap configured to be positioned within thechamber of the cap holder, the antiseptic cap comprising a sidewallforming a cap chamber and an antiseptic substance within the capchamber; and a strip extending over and forming a seal with each of thecap holders of each of the at least two cap assemblies, the stripcomprising a perforation configured to allow a user to individuallyseparate one or more of the at least two cap assemblies from the strippackage along the perforation such that the seal with each of the one ormore separated cap assemblies is maintained, wherein the strip forms asecond seal with each of the at least two cap assemblies.
 42. The strippackage of claim 41, wherein a peel force capable of removing each ofthe at least two cap assemblies from the strip is less than two poundsof force.
 43. The strip package of claim 41, wherein the strip forms thesecond seal between the strip and each of the caps of each of the atleast two cap assemblies.
 44. The strip package of claim 41, whereineach of said second seals is arranged substantially concentric withrespect to each of said respective seals.
 45. The strip package of claim41, wherein the strip comprises an unsealed portion located between theseal and the second seal.